scholarly journals Cell-type selective targeted delivery of a recombinant lysosomal enzyme for enzyme therapies

2021 ◽  
Author(s):  
Andrew D. Baik ◽  
Philip Calafati ◽  
Xiaoli Zhang ◽  
Nina A. Aaron ◽  
Antonia Mehra ◽  
...  
Keyword(s):  
Lysosomal Enzyme ◽  
Targeted Delivery ◽  
Cell Type

scholarly journals Phagolysosome formation in normal and colchicine-treated macrophages.

1975 ◽  
Vol 142 (4) ◽  
pp. 903-913 ◽  
Author(s):  
E L Pesanti ◽  
S G Axline
Keyword(s):  
Acid Phosphatase ◽  
Lysosomal Enzyme ◽  
Peritoneal Macrophages ◽  
Cell Type ◽  
Inert Particles ◽  
Time Periods ◽  
Mouse Peritoneal Macrophages ◽  
Over Time

Intracellular lysosomal fusion has been evaluated in cultivated mouse peritoneal macrophages by measurement of transfer of acid phosphatase to polyvinyltoluene (PVT)-containing phagolysosomes. Enzyme transfer was found to be directly and significantly related to the uptake of PVT and to be independent of time allowed for phagolysosome formation over time periods of 15 min to 18 h. In addition, the extent of transfer of lysosomal enzyme to phagolysosomes was unaffected by treatment of the cells with 10(-6) M colchicine, a dose which eradicates morphologically identifiable microtubules in this cell type within 2 h. The data indicate that intracellular fusion of lysosomes with phagosomes in the macrophage does not require formed microtubules and suggest that fusion occurs promptly after interiorization of inert particles.

Abstract 12105: Targeted Delivery of Therapeutic Agents After Myocardial Infarction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Siva Sai Krishna Dasa ◽  
Marc E Seamen ◽  
Brent A French ◽  
Kimberly A Kelly
Keyword(s):  
Myocardial Infarction ◽  
Phage Display ◽  
Targeted Delivery ◽  
Cell Types ◽  
Phage Display Library ◽  
Border Zone ◽  
Cell Type ◽  
Cellular Targets ◽  
Cell Type Specific

Introduction: Current therapies for heart failure (HF) after myocardial infarction (MI) only slow the progression of LV remodeling and have little capacity to regenerate cardiac muscle lost to MI. To expedite targeted delivery of regenerative therapies post-MI, we hypothesized that suitable targets could be identified by biopanning the heart with a phage display library in a mouse model of MI. Methods: A phage display library was biopanned in vivo to identify peptides specific for the infarct/border zone 4 days post-MI. Fluorescence molecular tomography (FMT) followed by tissue immunofluorescence was performed to interrogate the specificity of phage groups and individual clones with targeted phage at VT680 and neg control phage at VT750. The VT680 fluorophore on the targeted phage clones was then used to identify the cellular targets of those clones by counter-staining with antibodies against cell types of interest. Results: We identified phage clones specific for endothelium, cardiomyocytes, inflammatory fibroblasts and c-Kit+ cells present in the border zone post-MI. Liposomes conjugated with different cell type specific peptides had different accumulation rates in the post-infarct heart as visualized by FMT imaging (Fig. 1a). Immunofluorescence analysis demonstrated cell-type specific association of the targeted liposomes with cells expressing c-Kit, CD31 and Hrnr (Figs. 1b&c). We have also been successful in remote loading of anti-apoptotic and immune suppresive drugs into these liposomes and are currently studying their effect in mice after MI. Conclusions: Peptides identified by this screen enable the targeting of different cell types present in the border zone with different drugs. Identifying the molecular binding partners for these peptides may yield insight into the various events/pathways that evolve after a myocardial infarction.

scholarly journals Co-Opting Host Receptors for Targeted Delivery of Bioconjugates—From Drugs to Bugs

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1479
Author(s):  
Kristen M. Tummillo ◽  
Karsten R.O. Hazlett
Keyword(s):  
Antibiotic Resistance ◽  
Targeted Delivery ◽  
Bacterial Infections ◽  
Vaccine Development ◽  
Bacterial Species ◽  
Cell Type ◽  
Cancer Treatments ◽  
Functional Elements ◽  
The Brain ◽  
Advanced Treatments

Bioconjugation has allowed scientists to combine multiple functional elements into one biological or biochemical unit. This assembly can result in the production of constructs that are targeted to a specific site or cell type in order to enhance the response to, or activity of, the conjugated moiety. In the case of cancer treatments, selectively targeting chemotherapies to the cells of interest limit harmful side effects and enhance efficacy. Targeting through conjugation is also advantageous in delivering treatments to difficult-to-reach tissues, such as the brain or infections deep in the lung. Bacterial infections can be more selectively treated by conjugating antibiotics to microbe-specific entities; helping to avoid antibiotic resistance across commensal bacterial species. In the case of vaccine development, conjugation is used to enhance efficacy without compromising safety. In this work, we will review the previously mentioned areas in which bioconjugation has created new possibilities and advanced treatments.

Targeted delivery of Chil3/Chil4 siRNA to alveolar macrophages using ternary complexes composed of HMG and oligoarginine micelles

Nanoscale ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 933-943 ◽  
Author(s):  
Moonhwan Choi ◽  
Haeyoon Jeong ◽  
Sol Kim ◽  
Minkyung Kim ◽  
Minhyung Lee ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Delivery System ◽  
Alveolar Macrophages ◽  
Targeted Delivery ◽  
Ternary Complexes ◽  
Specific Gene ◽  
Gene Delivery System ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific

Cell-type-specific genes involved in disease can be effective therapeutic targets; therefore, the development of a cell-type-specific gene delivery system is essential.

Unraveling Cell-Type-Specific Targeted Delivery of Membrane-Camouflaged Nanoparticles with Plasmonic Imaging

Nano Letters ◽  
2020 ◽  
Vol 20 (7) ◽  
pp. 5228-5235
Author(s):  
Xiaodong Xie ◽  
Xingjie Hu ◽  
Qian Li ◽  
Min Yin ◽  
Haiyun Song ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Cell Type ◽  
Cell Type Specific ◽  
Plasmonic Imaging

Genetic engineering of a lysosomal enzyme fusion protein for targeted delivery across the human blood-brain barrier

2007 ◽  
Vol 99 (2) ◽  
pp. 475-484 ◽  
Author(s):  
Ruben J. Boado ◽  
Yun Zhang ◽  
Yufeng Zhang ◽  
Chun-fang Xia ◽  
Yuntao Wang ◽  
...  
Keyword(s):  
Genetic Engineering ◽  
Fusion Protein ◽  
Blood Brain Barrier ◽  
Human Blood ◽  
Lysosomal Enzyme ◽  
Targeted Delivery ◽  
Brain Barrier ◽  
Blood Brain ◽  
Enzyme Fusion

Ultrastructure of Fibroblast Cultures, Lymphocytes, and Liver in Mucopolysaccharidoses Types I, II, III, IV, and VI.

1970 ◽  
Vol 28 ◽  
pp. 204-205
Author(s):  
George Hug ◽  
William K. Schubert ◽  
Shirley Soukup
Keyword(s):  
Lysosomal Enzyme ◽  
Apparent Lack ◽  
Fibroblast Cultures ◽  
Lysosomal Diseases ◽  
Disease Specificity ◽  
Deficient Activity

McKusick subdivided the syndrome of mucopolysaccharidoses into six types according to clinical, roentenographic, and genetic criteria and to the kind of mucopolysaccharide(s) excreted in the urine (1). Deficient activity of a lysosomal enzyme, (β-galactosidase, has recently been reported in types I, II and III of mucopolysaccharidoses as well as in generalized gangliosidosis (2). This apparent lack of disease specificity makes the enzymatic deficiency difficult to interpret. Nevertheless, the involvement of a lysosomal enzyme tends to characterize these disorders as lysosomal diseases.

Ultrastructural Correlations between Clonal Human Tumor Colonies and in Vivo Neoplasms

1982 ◽  
Vol 40 ◽  
pp. 210-211
Author(s):  
M.J. Murphy ◽  
R.R. Price ◽  
J.C. Sloman
Keyword(s):  
Cultured Cells ◽  
Human Tumor ◽  
Cell Type ◽  
Tumor Mass ◽  
Initial Cell ◽  
Cloning Assay ◽  
Human Tumor Cloning ◽  
The Relationship

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.

Some Observations on Changes in Denervated Taste Buds of Circumvallate Papillae of Rabbits

1969 ◽  
Vol 27 ◽  
pp. 308-309
Author(s):  
Sunao Fujimoto ◽  
Raymond G. Murray ◽  
Assia Murray
Keyword(s):  
Taste Buds ◽  
Taste Bud ◽  
Cell Type ◽  
Dark Cells ◽  
Type Iii ◽  
Circumvallate Papillae ◽  
Taste Bud Cells ◽  
Light Cells

Taste bud cells in circumvallate papillae of rabbit have been classified into three groups: dark cells; light cells; and type III cells. Unilateral section of the 9th nerve distal to the petrosal ganglion was performed in 18 animals, and changes of each cell type in the denervated buds were observed from 6 hours to 10 days after the operation.Degeneration of nerves is evident at 12 hours (Fig. 1) and by 2 days, nerves are completely lacking in the buds. Invasion by leucocytes into the buds is remarkable from 6 to 12 hours but then decreases. Their extrusion through the pore is seen. Shrinkage and disturbance in arrangement of cells in the buds can be seen at 2 days. Degenerated buds consisting of a few irregular cells and remnants of degenerated cells are present at 4 days, but buds apparently normal except for the loss of nerve elements are still present at 6 days.

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